Cerebral interleukin-6 is neuroprotective during permanent focal cerebral ischemia in the rat.
Interleukin-6 (IL-6) is a neurotrophic cytokine expressed in both neurons and glia. The present study shows that cerebral ischemia produced by permanent occlusion of the middle cerebral artery (MCAO) produces a dramatic increase in IL-6 bioactivity in the ischemic hemisphere within 2 hours of MCAO (167 +/- 55 IU versus sham: 50 +/- 35 IU), with further increases at 8 hours (3,456 +/- 1,162 IU) and 24 hours (6,088 +/- 1,772 IU). In a separate series of experiments, intracerebroventricular injection of recombinant IL-6 (3,100 or 31,000 IU) significantly reduced ischemic brain damage after MCAO (to 52% and 65% of controls, respectively). The large increase in endogenous IL-6 bioactivity in response to ischemia, together with the marked neuroprotection produced by exogenous IL-6 suggest that this cytokine is an important endogenous inhibitor of neuronal death during cerebral ischemia.
Loddick
S A
SA
School of Biological Sciences, University of Manchester, United Kingdom.
Turnbull
A V
AV
Rothwell
N J
NJ
D000818:Animals; D001831:Body Temperature; D016923:Cell Death; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D015850:Interleukin-6 / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000473:pathology*; D007700:Kinetics; D008297:Male; D009474:Neurons / Q000502:physiology*; D018696:Neuroprotective Agents; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology
D015850:Interleukin-6; D018696:Neuroprotective Agents; D011994:Recombinant Proteins